Hypertension (HTN) is a public health menace contributing up to 45% of cardiovascular diseases (CVD) deaths and 51% of stroke deaths.[1] In India up to 33% of urban and 25% of the rural population are afflicted with the disease.[2] Attainment of blood pressure (BP) goals in the population at large is a major challenge and area of focus of health systems worldwide. Over the years, BP targets have been continuously redefined as the armamentarium of drugs has expanded. The recently published the American College of Cardiology/American Heart Association (ACC/AHA) 2017 HTN guidelines advocate a paradigm shift in the way we manage abnormal BP.[3]

Evolution of Blood Pressure Definitions and Goals

HTN has evolved historically from being considered “essential” to a malady about eight decades back. One of the earliest evidence can be dated back to 1959, when Build and Blood Pressure Study[4] (of around 5 million adults insured by 29 companies) revealed increased cardiovascular (CV) risk with high BP. These findings were further substantiated in 1960 by several reports from the Framingham Heart Study.[5] It was only after the development of orally effective thiazide and thiazide-like compounds in 1957, beneficial effects of treating severe and moderately severe HTN could be demonstrated in first multi-center HTN treatment trial (VA Co-operative Research study on HTN phase I and II)[6],[7] in 1967 and 1970. These developments led to the next milestone, i.e., NHLBI publishing its first report of the Joint National Committee (JNC) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure[8] in 1977. From 1977 to 2014, JNC has published eight reports providing recommendations for therapy every 3–5 years [Figure 1]. Purpose of these recommendations was to assist the practicing community and improve prevention, awareness, treatment, and control of high BP.

Based on limited trial data available at the time, JNC 1[8] report recommended treating diastolic BP (DBP) with drug therapy only when above 105 mmHg. For DBP 90–104 mmHg, an individualized approach based on risk factors was advised. No recommendation for treating systolic HTN was given. The recommended drug strategy was a “stepped care” approach beginning with thiazide-type diuretic and adding other drugs if needed. With the availability of further data from larger clinical trials, recommendations became increasingly aggressive and specific. JNC 2 report[9] in 1980 suggested the first classification of HTN based on DBP only and advocated drug therapy for moderate and severe HTN (DBP >104) and mild HTN (DBP-90–104) with target organ damage or increased CV risk. The Hypertension Detection and Follow-Up trial[10] published in 1979 was the first study to demonstrate a mortality benefit of goal-directed, stepped care BP treatment compared to usual care. The study established the practice of “stepped care approach to achieve BP goal” which became the norm of HTN treatment strategy ever since. This study also lowered the BP goal to DBP <90 mmHg. Systolic hypertension in the elderly program trial[11] (SHEP, 1991) was the first randomized control trial to show benefits of treating isolated systolic HTN which was earlier considered benign. Based on this JNC 5[12] (in 1993) emphasized the importance of systolic HTN and also proposed a new classification based on systolic BP (SBP). Drug therapy was recommended for patients with SBP of 140–149 mmHg and DBP of 90–94 mmHg after introducing lifestyle modifications and those with target organ disease or other risk factors. The BP goal was <140/90 mmHg. The lower target of 130/85 mmHg was allowed with due regard for CV function, especially in older persons. JNC 6[13] (in 1997) placed more emphasis on absolute risk and benefit and used risk stratification as part of the treatment strategy. In persons with high normal BP deemed to be at high risk (target organ damage/clinical CV disease and/or diabetes with or without other risk factors), initiation of drug therapy was recommended if BP remained >140/90 mmHg after lifestyle modifications. Due to the absence of clinical trial data, in contrast to JNC 6, JNC 7[14] (in 2003) did not use global risk assessment in making treatment decisions. The concept of “prehypertension” which was not considered as a disease category, was introduced for the first time in JNC 7 with an idea that earlier adoption of healthy lifestyle may reduce progression to HTN. Furthermore in JNC 7, Stage 3 HTN was no longer used since it had similar management strategies with stage 2 HTN. Drug therapy was recommended for persons with BP >140/90 mmHg after lifestyle interventions and for BP >130/80 mmHg for patients with diabetes or chronic kidney disease. The latest addition, JNC 8[15] was published in 2014. The primary difference from JNC 7 is that this report raised target SBP goals from 140 to 150 mmHg in subjects aged ≥60 years while eliminating recommendations for tighter control in persons with diabetes or chronic kidney disease. The observed difference in recommendations of JNC 7 and 8 stems from the fact that JNC 8 relied on systemic review of randomized controlled trials only and omitted data from nonrandomized and observational studies.

Although DBP goal was established as 90 mmHg in the late 1970s and later confirmed by HOT study,[18] the goal BP for systolic HTN has been a matter of much debate.

“lower Is Better” – Sprint - Ing to the Future

Before publication of SPRINT trial, multiple studies had tried to evaluate lower BP goals but without success. The HOT,[18] VALUE,[19] ACCORD,[20] and HOPE-3[21] were prominent ones that had failed. Based on the contemporary evidence, JNC VIII guidelines had relaxed BP targets in diabetics, chronic kidney disease, and prescribed lenient BP goal (<150/90) in the elderly as alluded to before.[15]

The SPRINT trial set the ball rolling for the aggressive lowering of BP. In this large randomized trial (n = 9361), hypertensive patients (age >50 years) with high CV risk (manifest or subclinical CVD), were randomized to two SBP goals of <140 mmHg or <120 mmHg.[22] The study had to be stopped early due to significant reduction in primary endpoint (composite of CV death, nonfatal myocardial infarction or stroke, hospitalization for heart failure or acute coronary syndrome) in intensive BP control arm. Unlike previous studies, patients randomized to aggressive BP goals had a significant reduction in major CV events by 25% and mortality by 23% at a median follow up of just over 3 years. Although the absolute risk reduction was less, the number needed to treat to prevent a primary outcome event and CV death were impressive at 61 and 72, respectively. Such promising data from a rigorously conducted randomized trial were hard to ignore and stirred a debate on their generalization to the entire population.[23]

2017 American College of Cardiology/american Heart Association Guidelines-A Game Changer!!

Recently, ACC and AHA jointly in association with other bodies in their extensive guideline have radically redefined the classification of abnormal BP as well as BP goals.[3] We briefly discuss important changes affecting evaluation management of HTN in routine clinical practice.

A new classification of hypertension

Perhaps the most visible and radical change has been the reclassification of abnormal BP [Figure 2]. A new category of “Elevated BP” has been added, and previously defined stages of HTN have been changed. The previously used classification of “Pre-HTN” (SBP-120–139 mmHg/DBP-80–89 mmHg) has been abolished.

Figure 2: Revised Classification of Blood pressure by American College of Cardiology/American Heart Association 2017 guidelines and it's comparison with previously used JNC 7 Stages

Henceforth, SBP >130 mmHg or DBP >80 mmHg would be categorized as HTN. The rationale for such reclassification is provided by progressive increase in the hazard ratio (HR) of stroke and coronary heart disease as one moves from normal BP to elevated BP (HR - 1.1–1.5) and from there to Stage 1 HTN (HR - 1.5–2.0). A patient whose SBP and DBP values fall in different categories should be assigned to the category with higher value. The BP readings used for classification should be an average of two or more readings instead of relying on a single value.

Emphasis on accurate measurement of BP

Another major emphasis of the guideline has been accurate measurement as well use of average reading. Key elements of checklist for accurate measurement of BP include the “7S” and are summarized in [Figure 3]. Strong emphasis has been placed on the use of multiple measurements for deciding BP status of the patient as BP is a continuous variable. Utilizing an average of two or more readings on two or more occasions minimizes the chances of random error.

Liberal use of out of office blood pressure – Ambulatory Blood Pressure Monitoring or Home Blood Pressure Monitoring

The guideline advocate use of either form of out of office BP measurement - Home BP monitoring (HBPM) or Ambulatory BP monitoring (ABPM) for both diagnosis and management of HTN. These recommendation are on similar lines to 2011 NICE guidelines for management of HTN.[24] Although ABPM is accepted as a better form of out of office measurement and has a large body of data in support, HBPM is a more practical form of measurement. Emerging data support the use of HBPM in achieving better control of BP.[25] Both the methods help in diagnosing “White coat hypertension” and “Masked hypertension” in untreated patients. For patients already on therapy, they aid in diagnosing “White coat effect” and “Masked uncontrolled hypertension.” The convergence between clinic BP readings and other out of office measurements is given in [Figure 4].

Although present only in the minority (10%), multiple clinical scenarios should alert the physician to search for them. These include the onset of HTN at early age <30 years, uncontrolled or difficult to control HTN, abrupt onset of HTN, worsening BP goals in a previously controlled patients, hypertensive crisis, diastolic HTN in old age, persistent hypokalemia, and mismatch of end-organ damage with the severity of HTN. Commonly used screening tests include renal Doppler ultrasound, plasma aldosterone/renin ratio, urine screen for drugs, Berlin questionnaire, and less commonly 24 h urinary metanephrines.

Nonpharmacological interventions are important at all stages

Nonpharmacological interventions are the cornerstone of management in Stage 1 HTN and play a synergistic role in managing stage 2 HTN. Their overall benefits are at best modest (2–10 mmHg reduction) with maximum antihypertensive effect with dietary approaches to stop HTN (DASH) diet. Major interventions with proven long-term benefit include weight loss, DASH diet, increased physical activity, salt restriction, potassium supplementation, and moderation of alcohol.

Incorporation cardiovascular risk assessment in decision-making

The decision to incorporate global CVD risk assessment in clinical decision-making comes from the premise that for an equivalent reduction in BP, more CVD deaths are prevented in high-risk individual and older individual vis-a-vis low-risk and young patients. As a corollary, the number needed to treat would be lower in the former.

The guidelines recommend the ACC/AHA pooled cohort equation for estimating 10 years atherosclerotic CVD and use a 10% threshold for initiation of pharmacotherapy. In patients with stage 1 HTN, pharmacotherapy is indicated if their 10 years risk is >10% or they have manifest CVD (coronary heart disease, stroke, or congestive heart failure). The limitation of this equation is that it is not applicable for very elderly (>79 years) and it overestimates risk in Asians. The Joint British Society 3 risk score or WHO-ISH modified risk scores for south-east Asian region are suited better for Indian population and may be used instead for our patients.[26] Pharmacotherapy is indicated in all patients of stage 2 in conjunction with lifestyle modification in sync with previous recommendations.

Blood pressure targets are now aggressive

Meta-analyses and systematic reviews of multiple trials comparing an aggressive versus standard BP goals have shown a consistent reduction in stroke, coronary events, and major adverse CV events.[27],[28] Although, these data have demonstrated a linear relationship between achieved SBP and CV risk reduction and there would be patient subgroups who would benefit from an achieved SBP <120 mmHg, the heterogeneity of trials and inclusion criteria preclude applicability of such stringent goals to the general population. Keeping this in view, the guidelines recommend a BP target of 130/80 mmHg in patient who are on treatment for HTN.

Beta-blockers are still out of first-line therapy

Thiazide diuretics, calcium channel blockers, angiotensin converting enzyme inhibitors (ACE-I), and angiotensin receptor blockers (ARBs) still continue to be the frontline drugs for initiation of pharmaco therapy. All these classes of drug have shown CV risk reduction when compared to placebo in randomized trials. Beta-blockers continue their relegated status due to a negative impact on central aortic BP and lack of protection from stroke. The overall aim is to achieve sustainable BP reduction for trimming CV risk and choice of agents individual agent is of less concern. Following initiation of therapy, a monthly follow up is needed until target BP goals are achieved. HBPM, ABPM, team-based care, and telehealth strategies all should be used based on availability and familiarity of physician.

Chlorthalidone is the first line diuretic

Data from ALLHAT study has shown the superiority of thiazide diuretic chlorthalidone over CCB and ACE-I in the prevention of HF.[29] Chlorthalidone also scored over ACE-I in stroke and overall BP reduction. Although not relevant to our region, ACE-I are less effective than other classes in black patients for CV risk reduction. ARB though have better tolerance in terms of lower cough and angioedema, there is a paucity of data showing their advantage over ACE-I.

Monotherapy versus upfront combination therapy

The guidelines recommend upfront initiation of two-drug combination in patients with Stage 2 HTN with BP >20/10 mmHg above their goal. The choice of fixed-dose combination or separate tablets is left at the discretion of treating physician. The rationale for such a strategy rests on the facts that majority of the patients would need two or more drug for attaining BP goals and those with every high BP have also high CV risk. In addition, studies of fixed-dose combination have revealed better compliance and greater BP lowering.[30] The hitherto recommended “Stepped Care Approach” is now reserved for very elderly, those with drug-associated hypotension and other side effects.

Conclusion

The global burden of CVD will continue to rise owing to an aging population and increasing prevalence of risk factors. HTN being a major contributor to CVD conundrum needs to be tackled urgently and aggressiwwvely. Despite the availability of a easy to use ubiquitous diagnostic tool (sphygmomanometer) and safe drugs, the incidence paradoxically continues to rise. In this context, the current HTN guidelines take the challenge head-on. By committing to an earlier, aggressive and upfront robust treatment strategy, it cannot be anything less than a step in positive direction. On the surface, though the new classification will increase the number diagnosed with HTN, it has provided checks and balances for not to substantially increase the number treated for it. With the recent provision of low-cost drugs by authorities (Amrit Pharmacies by health ministry), the financial burden imposed by the implementation of the guideline will be substantially alleviated. However, implementation of ” the ten commandments” from the guideline hold the definite promise of reduction in CVD burden in the long term [Figure 5].

Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension detection and follow-up program cooperative group. JAMA 1979;242:2562-71.

Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the systolic hypertension in the elderly program (SHEP). SHEP cooperative research group. JAMA 1991;265:3255-64. [PUBMED]